Reactive oxygen species (ROS) can cause major damage to cells by oxidizing lipids, proteins, carbohydrates and DNA in cells and tissues. This undesirable oxidation results in membrane damage, protein modification and DNA impairment that can give rise to death of cells and tissues. ROS induced oxidative stress is associated with pathological diseases like atherosclerosis (Oliviera et al., FASEB J. 19, 278, 2005; Kevil, FASEB J. 18, 1321, 2004), diabetes type 2, neurodegenerative diseases (Bergamini, Curr. Pharm. Des. 10, 1611, 2004; Masella, J. Nutr. Biochem. 16, 577, 2005) and cancer (Brown, Breast Cancer Res. 3, 323, 2001).
Glutathione is the major cellular anti-oxidant. Under normal conditions, 99% of the total glutathione is in the form of reduced glutathione, GSH. Protection against ROS is obtained by forming oxidized glutathione (GSSG) or other GSH conjugates (Bergamini, Curr. Pharm. Des. 10, 1611, 2004). The formed GSSG can be enzymatically reduced by glutathione reductase or alternatively excreted out of the cell to maintain the high cellular GSH/GSSG ratio (Dickinson, Ann. N Y. Acad. Sci. 973, 488, 2002). Glutathione is thus highly important for cellular function, wherein imbalance in cellular GSH/GSSG ratio is associated with various pathological processes such as arthritis, atherosclerosis, type 2 diabetes, cancer and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (Liu, Ann. N.Y. Acad. Sci. 1019, 346, 2004). It is therefore highly important to find means for up-regulating cellular glutathione level.
GSH synthesis in cells is normally regulated by feedback inhibition of the rate-limiting enzyme glutamate-cysteine-ligase (Anderson, Chem. Biol. Interact. 112, 1, 1998). Cysteine is known as a precursor for glutathione biosynthesis and its concentration controls the rate of glutathione biosynthesis.
N-acetylcysteine (NAC) is used as a food supplement aimed to supply cells with cysteine thereby increasing glutathione cellular level. However, NAC penetration to the brain and other tissues is limited. Pyrrolidine dithiocarbamate (PDTC) is known to have antioxidant properties and is considered as a potential NF-κB inhibitor (Kim et al., J. Neurochem. 72, 1586, 1999).
Allicin, the garlic primary active compound, is a small molecule that freely permeates through phospholipids bilayers. The allicin molecule interacts with different thiol containing compounds via the thiol functional groups to form various metabolites containing disulfide bonds, such as S-allylmercaptoglutathione (GSSA) or S-allylmercaptocysteine (CSSA) (Lawson in Phytomedicines of Europe: Their Chemistry and Biological Activity, A.C.S., Washington D. C., 176, 1998; Miron, Biochim. Biophys. Acta 1463, 20, 2000).
Japanese patent No. 62063517 discloses pharmaceutical compositions of cysteine derivatives for the treatment of liver diseases. Amongst the derivatives disclosed in JP-62063517 is S-allylmercapto-N-acetylcysteine (ASSNAC).

There is an unmet need for effective and safe prevention and treatment of oxidative stress in vivo. Furthermore, there is an unmet need for readily bioavailable and non-toxic agents to elevate the natural body levels of anti-oxidant glutathione.